The National Institute of General Medical Sciences (NIGMS) announces a Request for Applications for the development of a central knowledge and data resource (henceforth referred to as the “K-12 Resource”) for Escherichia coli strain K-12, related strains, and their phages and mobile genetic elements (henceforth referred to as the “K-12 Group”). The K-12 Resource will organize and increase the utility of sequence, sequence annotation, high throughput data, data mining algorithms, mathematical models, structural and functional data, and legacy information related to the biology of the K-12 Group, while identifying and filling any gaps in informatics activities needed by the research community. The K-12 Resource will provide access to existing sources, as well as internally generated data and information. The K-12 Resource will be responsive to the needs of both experimental and computational researchers while also providing the community with a K-12 centric forum for news and announcements.

This announcement specifies a single award with an initial commitment of approximately $800,000 Total Costs in FY 06.

The U24 Research Resource Cooperative Agreement mechanism will be used.

New groups as well as owners of current database resources that provide part of what is sought in this solicitation are encouraged to compete for the opportunity; current database projects may seek to expand their scope to encompass the objectives defined below. Eligible institutions include domestic institutions, for-profit or non-profit organizations, public or private institutions, such as universities, colleges, hospitals, and laboratories, units of State and local governments, and eligible agencies of the Federal government. Foreign institutions may participate as collaborating institutions. Individuals with the skills, knowledge, and resources necessary to carry out the proposed research are invited to work with their institution to develop applications for support.

Eligible Principle investigators include individuals from underrepresented racial and ethnic groups as well as individuals with disabilities.

Applications must be prepared using the PHS 398 research grant application instructions and forms. The PHS 398 is available at http://grants.nih.gov/grants/funding/phs398/phs398.html in an interactive format. There is no limit to the number of scientifically distinct applications submitted from a sponsoring institution. For further assistance contact Grants Info, Telephone (301) 435-0714, Email: GrantsInfo@nih.gov.

Telecommunication for the hearing impaired is available at TTY 301-451-5936

The objective of this announcement is the development of a central knowledge and data resource (henceforth referred to as the “K-12 Resource”) for Escherichia coli strain K-12, related strains, and their phages and mobile genetic elements (henceforth referred to as the “K-12 Group”). The K-12 Resource will provide a unified, high quality, single point of access to the data, information, and software tools that have been developed over the past six decades on the K-12 Group and thus leverage the considerable investment of public and private research funds in this suite of model organisms. In particular, the K-12 Resource will complement recent Federal programs to provide integrated databases of information on other microbes, including agents of disease and bioterrorism that are closely related to E. coli K-12. It is expected that all microbial database efforts will benefit by transparent links to the data and computational tools that exist or will be constructed for the K-12 Resource.

The proposed K-12 Resource will develop a central knowledge and data resource through the following functionalities:

A search and display interface friendly to users of varying familiarity with the K-12 Group of model organisms;

Definitive sequence and genome annotation data and a plan for continuous curation of the genome features of the relevant strains and phages;

Access to new and pre-existing software tools for analyzing and representing diverse data types from the experimental literature;

A forum for ongoing discussion about developments in K-12 Group biology.

The K-12 Resource will have a Steering Committee as the main policy making body. The Committee will include Scientist Administrators from the NIH and possibly other Federal agencies, the PI and key personnel, and outside experts from the appropriate user groups.

The informatics needs of the relevant research communities can be expected to evolve as the science progresses. The K-12 Resource is expected to have the flexibility to adapt to changing needs.

The funding and term of award reflect the expectation that the final form and scope of the K-12 Resource may only be apparent after a few years of effort and input from the community, at which time further funding may be sought.

Background

More is known about Escherichia coli strain K-12, its closely related strains, relatives, and their phages, than any other group of organisms. This knowledge has provided biomedical science much of its information on fundamental molecular biology, metabolic pathways, gene and enzyme regulation, and detailed biochemical and biophysical mechanistic understanding of macromolecules; of late these studies have expanded to include computational modeling of the large-scale organization and dynamics of its component systems. This wealth of historical and current information continues to provide the larger biomedical research community with a context in which to understand, through comparative studies, the functioning of other organisms, and bacteria in particular.

However, the research community has identified a pressing need to bring together the multiple sources of existing knowledge and rapidly accumulating genome-wide data and to make this information optimally usable. For many model organism research communities, this need is fulfilled by community genome databases such as Saccharomyces Genome Database, WormBase, and FlyBase for the yeast, worm, and fly communities, respectively. In March 2003, NIGMS organized a meeting of researchers with expertise and interest in E. coli K-12, as well as other microorganisms, and database experts to discuss the informatics needs of the K-12 Group. A subcommittee of this meeting composed a White Paper on these needs, with recommendations (URL: http://www.nigms.nih.gov/news/reports/ecoli.html). In brief, the consensus was that although there are a number of databases that currently focus on or include E. coli K-12 data and bioinformatics tools, there are significant gaps in what they cover, they are generally not well integrated with one other, they are of variable quality and utility, and there is no single point of entry for users. This subcommittee recommended the establishment of a resource that organizes and updates available information and presents it in a manner comparable to that of other model organism databases. Although no particular structure for such a resource was defined by this subcommittee, the goal of the herein proposed K-12 Resource is to address the broad and specific issues raised by the White Paper.

In addition to serving the needs of the basic research communities, the K-12 Resource will provide, through its coordination with other microbial databases, important foundations of knowledge for pathogenic microbes, including those of concern for bioterrorism. Such coordination will insure that the Federal investment in microbial research is optimally leveraged to generate new knowledge and protect the public.

Specific Research Objectives

There are four key areas that the applications for the K-12 Resource must address:

Content: the sources of knowledge, data, and tools to be provided and integrated;

Database and website interface design, development and continuing support, with an emphasis on interoperability with other relevant databases;

Management, to include plans to integrate internal and external resources and provide quality assurance; and

Community relationships: outreach to the end user research communities.

Content

The K-12 Resource will include information specific to E. coli K-12 as well as relevant data from strains C and B, and information and data on the principal phages and plasmids that contribute to our basic knowledge of gene transactions, self-assembly processes, and bacterial functioning through the host-parasite relationship. The content must be current, documented, and reflect uncertainties. The application will provide a plan for:

Archiving definitive sequence and sequence variations;

An annotation infrastructure providing ongoing curation of:

• Sequence features, both experimentally determined and predicted;
• Functional and structural assignments of sequence features with documentation and links to the experimental literature and to specialized review and curation sources;
• Phylogenetic comparisons of protein/RNA families, gene order and the like;

A multitude of databases, of varied coverage and utility, provide information on the K-12 Group
(cf. http://www.uni-giessen.de/~gx1052/IECA/ieca.html). It is a goal of this solicitation that the Resource create a structure and management plan that will 1) integrate the most valuable of these sources; 2) provide complementary information and tools; 3) coordinate with other related microbial database resources to maximize the utility of the information and services; and 4) provide for timely updates and quality assurance. Among the possible structures that could accommodate these needs are data warehouses and database federation using web services. Each has operational advantages. Alternatively, a combination of the two may be the most efficient and practical. The final interface should present different forms and types of data in a convenient format for the user while preserving attribution of the data sources. It is not the intention of this solicitation to prescribe any particular structure, and innovation in this difficult task is expected. Researching the best solution may occupy the early term of the project.

A key requirement for the K-12 Resource is that it serve a wide spectrum of users whose needs and expertise may be different. This requirement must be satisfied with a website that emulates, or preferably improves upon, the best of existing model organism database interfaces. Among the characteristics of such interfaces are: an intuitive, logical structure, simplicity in layout, clear paths to diverse datasets, and user friendly analytic tools. Where possible, the K-12 Resource should build upon tools developed by other related resources, e.g., the components developed for the Generic Model Organism Database Construction Set (http://www.gmod.org/). In order to promote utility across other resources the database will coordinate with other related informatics resources to develop or adopt protocols for standardization of syntax, ontologies and vocabularies, and data representation. It is essential that data can readily be shared. Participation in the Gene Ontology (GO) consortium is required, and documented agreements for coordination with other U.S. funded resources with which it overlaps or shares common spheres of data. In particular, there will need to be coordination with the National Institute of Allergy and Infectious Diseases (NIAID) ERIC program (http://www.niaid.nih.gov/dmid/genomes/brc/PDF/eric.pdf), which focuses on closely related organisms of pathological interest.

The application should explain how efficient and unencumbered access to the K-12 Resource will be maintained. A method for freely downloading large datasets from the K-12 Resource, so that users can acquire and analyze all or large parts of the data, should be included. The capacity of the K-12 Resource to expand to accommodate an increase in database entries and information will be described. The K-12 Resource should be easily accessible with multiple methods of querying, including simple web interfaces for common standard queries and tools for more complex queries.

Management

The organization, updating and maintenance of the E. coli K-12 Resource will require a management structure that supports the goal of providing timely updating of the informatics resources, and quality assurance. To achieve this, the K-12 Resource must, to the degree possible, develop cooperative relationships with owners of existing sources of data and related information. Examples are the NCBI, the Coli Genetics Stock Center, the NIAID ERIC resource, and other domestic and foreign individual and collective sources, as well as other model organism resources. Applicants should explain how the projects to be supported by this award will coordinate with related projects supported by other funding. Some examples are the organization of meetings for annotation and other specialized community purposes, meetings to coordinate database interoperability efforts, and plans to disseminate information on the K-12 Resource. To aid in this goal the K-12 Resource will identify a Steering Committee that will provide overall policy guidance for the K-12 Resource; this Committee should reflect the diversity of expected users of the K-12 Resource.

The application should discuss how the K-12 Resource will set priorities to accomplish the requirements above within the limitations of the proposed budget. The application should provide specific plans for operating in a cost-effective manner.

Community Relationships

The E. coli K-12 Resource is expected to operate as a general forum for a multitude of investigators; some will be content experts in the K-12 Group, and their cooperation will be critical in keeping the K-12 Resource content current. Although the Steering Committee will play a valuable role in providing scheduled, periodic input to the K-12 Resource, ongoing discussions, announcements and observations from the general community also should be accommodated within the K-12 Resource.

This funding opportunity will use the U24 Research Resource Cooperative Agreement award mechanism(s). As an applicant, you will be primarily responsible for planning, directing, and executing the proposed project.

This funding opportunity uses the just-in-time budget concepts. It also uses the non-modular budget format described in the PHS 398 application instructions (see http://grants.nih.gov/grants/funding/phs398/phs398.html). A detailed categorical budget for the "Initial Budget Period" and the "Entire Proposed Period of Support" is to be submitted with the application.

The NIH U24 is a cooperative agreement award mechanism. In the cooperative agreement mechanism, the Principal Investigator retains the primary responsibility and dominant role for planning, directing, and executing the proposed project, with NIH staff being substantially involved as a partner with the Principal Investigator, as described under the Section VI. 2. Administrative Requirements, "Cooperative Agreement Terms and Conditions of Award".

2. Funds Available

NIGMS intends to commit approximately 800,000 dollars total costs in FY 06 to fund a single grant in response to this RFA. An applicant may request a project period of up to three years and a budget for direct costs up to 500,000 dollars per year, exclusive of subproject indirect costs. Although the financial plans of the IC(s) provide support for this program, awards pursuant to this RFA are contingent upon the availability of funds and the receipt of a sufficient number of meritorious applications.

Facilities and administrative costs requested by consortium participants are not included in the direct cost limitation, see NOT-OD-05-004.

Section III. Eligibility Information

1. Eligible Applicants

1.A. Eligible Institutions

You may submit (an) application(s) if your organization has any of the following characteristics:

For-profit organizations

Non-profit organizations

Public or private institutions, such as universities, colleges, hospitals, and laboratories

Units of State government

Units of local government

Eligible agencies of the Federal government

Domestic Institutions

Foreign Institutions are not eligible to apply. Foreign institutions may, however, participate as collaborating institutions.

1.B. Eligible Individuals

Any individual with the skills, knowledge, and resources necessary to carry out the proposed research is invited to work with their institution to develop an application for support. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH programs.

Applications must be prepared using the most current PHS 398 research grant application instructions and forms. Applications must have a D&B Data Universal Numbering System (DUNS) number as the universal identifier when applying for Federal grants or cooperative agreements. The D&B number can be obtained by calling (866) 705-5711 or through the web site at http://www.dnb.com/us/. The D&B number should be entered on line 11 of the face page of the PHS 398 form.

The title and number of this funding opportunity must be typed on line 2 of the face page of the application form and the YES box must be checked.

Prospective applicants are asked to submit a letter of intent that includes the following information:

Descriptive title of proposed research

Name, address, and telephone number of the Principal Investigator

Names of other key personnel

Participating institutions

Number and title of this funding opportunity

Although a letter of intent is not required, is not binding, and does not enter into the review of a subsequent application, the information that it contains allows IC staff to estimate the potential review workload and plan the review.

The letter of intent is to be sent by the date listed at the beginning of this document.

Applications must be prepared using the PHS 398 research grant application instructions and forms as described above. Submit a signed, typewritten original of the application, including the checklist, and three signed photocopies in one package to:

Using the RFA Label: The RFA label available in the PHS 398 application instructions must be affixed to the bottom of the face page of the application. Type the RFA number on the label. Failure to use this label could result in delayed processing of the application such that it may not reach the review committee in time for review. In addition, the RFA title and number must be typed on line 2 of the face page of the application form and the YES box must be marked. The RFA label is also available at: http://grants.nih.gov/grants/funding/phs398/labels.pdf. Personal deliveries of applications are no longer permitted.

3.C. Application Processing

Applications must be received on or before the application receipt/submission date(s) described above (Section IV.3.A.). If an application is received after that date, it will be returned to the applicant without review. Upon receipt, applications will be evaluated for completeness by the CSR and responsiveness by the NIGMS. Incomplete and non-responsive applications will not be reviewed.

The NIH will not accept any application in response to this funding opportunity that is essentially the same as one currently pending initial review, unless the applicant withdraws the pending application. However, when a previously unfunded application, originally submitted as an investigator-initiated application, is to be submitted in response to a funding opportunity, it is to be prepared as a NEW application. That is, the application for the funding opportunity must not include an Introduction describing the changes and improvements made, and the text must not be marked to indicate the changes from the previous unfunded version of the application.

Although there is no immediate acknowledgement of the receipt of an application, applicants are generally notified of the review and funding assignment within eight (8) weeks.

All NIH awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement. The Grants Policy Statement can be found at http://grants.nih.gov/grants/policy/policy.htm.

Pre-Award Costs are allowable. A grantee may, at its own risk and without NIH prior approval, incur obligations and expenditures to cover costs up to 90 days before the beginning date of the initial budget period of a new or competing continuation award if such costs: are necessary to conduct the project, and would be allowable under the grant, if awarded, without NIH prior approval. If specific expenditures would otherwise require prior approval, the grantee must obtain NIH approval before incurring the cost. NIH prior approval is required for any costs to be incurred more than 90 days before the beginning date of the initial budget period of a new or competing continuation award.

The incurrence of pre-award costs in anticipation of a competing or non-competing award imposes no obligation on NIH either to make the award or to increase the amount of the approved budget if an award is made for less than the amount anticipated and is inadequate to cover the pre-award costs incurred. NIH expects the grantee to be fully aware that pre-award costs result in borrowing against future support and that such borrowing must not impair the grantee's ability to accomplish the project objectives in the approved time frame or in any way adversely affect the conduct of the project. See NIH Grants Policy Statement http://grants.nih.gov/archive/grants/policy/nihgps_2003/index.htm.

6. Other Submission Requirements

General Issues

Implementation Plan. Applications must include a time line and milestones for the development of the K-12 Resource; the execution may be complex due to the need to reach agreements with outside providers of information, to develop the public interface, to organize and develop procedures for input from the research communities and the Steering Committee, and to create de novo procedures and instruments for database construction.

Annual Meeting. Applications should include travel funds for the Principal Investigator and K-12 Resource personnel to attend a Steering Committee annual meeting in Bethesda, MD, to discuss progress and results.

Video/teleconferences. At times, particularly in the early term of the K-12 Resource, it may be necessary to have frequent consultation between the Steering Committee or its subcommittees and the PI. The application budget should provide funds to set up video conferencing via phone or computer links for this purpose. The Steering Committee and Program Director will coordinate the scheduling of these conferences on a schedule that will meet the needs of the K-12 Resource.

Letters of Collaboration. Arrangements by the PI to integrate various data and knowledge sources should be documented with letters specifically stating the terms of access; these may be provided as appendices.

Data and Resource Sharing Plans. Data sets, models and tools, including source code, will be made publicly available through the K-12 Resource portal according to NIH policy as listed below in “Plan for Sharing Research Data,” and “Sharing Research Resources,” and Section V.2.C and V.2.D.

Plan for Sharing Research Data

All applicants must include a plan for sharing research data in their application. The data sharing policy is available at http://grants.nih.gov/grants/policy/data_sharing. All investigators responding to this funding opportunity should include a description of how final research data will be shared, or explain why data sharing is not possible.

The reasonableness of the data sharing plan or the rationale for not sharing research data will be assessed by the reviewers. However, reviewers will not factor the proposed data sharing plan into the determination of scientific merit or the priority score. Since the purpose of the K-12 Resource is to provide data and other information to the scientific community, the investigator must describe briefly the expected schedule for data sharing, the format of the final dataset, the documentation to be provided, whether or not any analytic tools also will be provided, whether or not a data-sharing agreement will be required and, if so, a brief description of such an agreement (including the criteria for deciding who can receive the data and whether or not any conditions will be placed on their use), and the mode of data sharing (e.g., by mailing a disk or posting data on the K12 Resource website.) References to data sharing may also be appropriate in other sections of the application.

While the data sharing plan will not be considered in determination of the priority score, the plan (Section V.2.C) will be an important programmatic consideration in selecting the single awardee.

A software dissemination plan, if applicable, must be included in the application. There is no prescribed single license for software produced in this project. However, this initiative includes goals for software dissemination, and reviewers will be instructed to make comments on the dissemination plan relative to these goals:

1) The software generated by the K-12 Resource should be freely available to biomedical researchers and educators in the non-profit sector, such as institutions of education, research institutes, and government laboratories.

2) The terms of K-12 Resource-generated software availability should permit the commercialization of enhanced or customized versions of the software, or incorporation of the software or pieces of it into other software packages.

3) The terms of the K-12 Resource-generated software availability should include the ability of researchers outside the K-12 Resource and its collaborating projects to modify the source code for their own purposes. The K-12 Resource should stipulate that these modifications may be shared with other colleagues who have obtained the source code from the K-12 Resource, and should also be shared with the K-12 Resource. The application must include written statements from the officials of the applicant institutions responsible for intellectual property issues, to the effect that the institution supports and agrees to abide by the software dissemination plans put forth in the application. Typically the relevant responsible official will be in the applicant institution's office of technology transfer or intellectual property, as opposed to an academic official such as a department head or dean.

The adequacy of the resources sharing plan and any related data sharing plans will be considered by Program staff of the funding organization when making recommendations about funding applications. The effectiveness of the resource sharing will be evaluated as part of the administrative review of each non-competing Grant Progress Report (PHS 2590, http://grants.nih.gov/grants/funding/2590/2590.htm). See Section VI.3. Reporting.

Section V. Application Review Information

1. Criteria

Only the review criteria described below will be considered in the review process.

The following will be considered in making funding decisions:

Scientific merit of the proposed project as determined by peer review

Availability of funds

Relevance of program priorities

If funded, the terms and conditions of award will specify the need for a report from the Steering Committee following its annual meeting, and documentation of efforts to coordinate with other related Federally funded databases, e.g., ERIC and the Coli Genetics Stock Center, and summary data on the use of the K-12 Resource.

2. Review and Selection Process

Applications that are complete and responsive to the RFA will be evaluated for scientific and technical merit by an appropriate peer review group convened by NIGMS in accordance with the review criteria stated below.

As part of the initial merit review, all applications will:

Undergo a selection process in which only those applications deemed to have the highest scientific merit, generally the top half of applications under review, will be discussed and assigned a priority score.

Receive a written critique.

Receive a second level of review by the National Advisory General Medical Sciences Council.

The goals of NIH supported research are to advance our understanding of biological systems, to improve the control of disease, and to enhance health. In their written critiques, reviewers will be asked to comment on each of the following criteria in order to judge the likelihood that the proposed research will have a substantial impact on the pursuit of these goals. Each of these criteria will be addressed and considered in assigning the overall score, weighting them as appropriate for each application. Note that an application does not need to be strong in all categories to be judged likely to have major scientific impact and thus deserve a high priority score. For example, an investigator may propose to carry out important work that by its nature is not innovative but is essential to move a field forward.

1. Significance. Does this study address an important problem? If the aims of the application are achieved, how will scientific knowledge or clinical practice be advanced? What will be the effect of these studies on the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field? Will the proposed K-12 Resource address the needs of the diverse constituent research communities?

2. Approach. Are the conceptual or clinical framework, design, methods, and analyses adequately developed, well integrated, well reasoned, and appropriate to the aims of the project? Does the applicant acknowledge potential problem areas and consider alternative tactics? Are the plans for implementing the K-12 Resource optimally designed to solicit input from the research communities and is there adequate documentation of efforts to integrate existing resources?

3. Innovation. Is the project original and innovative? For example: Does the project challenge existing paradigms or clinical practice; address an innovative hypothesis or critical barrier to progress in the field? Does the project develop or employ novel concepts, approaches, methodologies, tools, or technologies for this area? Will the proposed K-12 Resource advance the state of the art in model organism databases in structure, content and design?

4. Investigators. Are the investigators appropriately trained and well suited to carry out this work? Is the work proposed appropriate to the experience level of the principal investigator and other researchers? Does the investigative team bring complementary and integrated expertise to the project (if applicable)?

5. Environment. Does the scientific environment in which the work will be done contribute to the probability of success? Do the proposed studies benefit from unique features of the scientific environment, or subject populations, or employ useful collaborative arrangements? Is there evidence of institutional support?

2.A. Additional Review Criteria: Not applicable

2.B. Additional Review Considerations

Budget: The reasonableness of the proposed budget and the requested period of support in relation to the proposed research. The priority score should not be affected by the evaluation of the budget.

2.C. Sharing Research Data

Data Sharing Plan: The reasonableness of the data sharing plan or the rationale for not sharing research data will be assessed by the reviewers. However, reviewers will not factor the proposed data sharing plan into the determination of scientific merit or the priority score. The presence of a data sharing plan will be part of the terms and conditions of the award. The funding organization will be responsible for monitoring the data sharing policy. Prior to award, program staff will review documentation of any proposed agreements on sharing information; the award will be contingent upon meeting the objectives for Database and Web Interface Design described in Section I under Specific Research Objectives.

A software dissemination plan, if applicable, must be included in the application. There is no prescribed single license for software produced in this project. However, this initiative includes goals for software dissemination, and reviewers will be instructed to make comments on the dissemination plan relative to these goals:

1) The software generated by the K-12 Resource should be freely available to biomedical researchers and educators in the non-profit sector, such as institutions of education, research institutes, and government laboratories.

2) The terms of K-12 Resource-generated software availability should permit the commercialization of enhanced or customized versions of the software, or incorporation of the software or pieces of it into other software packages.

3) The terms of the K-12 Resource-generated software availability should include the ability of researchers outside the K-12 Resource and its collaborating projects to modify the source code for their own purposes. The K-12 Resource should stipulate that these modifications may be shared with other colleagues who have obtained the source code from the K-12 Resource, and should also be shared with the K-12 Resource. The application must include written statements from the officials of the applicant institutions responsible for intellectual property issues, to the effect that the institution supports and agrees to abide by the software dissemination plans put forth in the application. Typically the relevant responsible official will be in the applicant institution's office of technology transfer or intellectual property, as distinguished from an academic official such as a department head or dean.

The adequacy of the resources sharing plan will be considered by Program staff of the funding organization when making recommendations about funding applications. Program staff may negotiate modifications of the data and resource sharing plans with the awardee before recommending funding of an application. The final version of the data and resource sharing plans negotiated by both will become a condition of the award of the grant. The effectiveness of the resource sharing will be evaluated as part of the administrative review of each non-competing Grant Progress Report (PHS 2590). See Section VI.3. Reporting.

3. Anticipated Announcement and Award Dates Not applicable

Section VI. Award Administration Information

1. Award Notices

After the peer review of the application is completed, the Principal Investigator will also receive a written critique called a Summary Statement.

If the application is under consideration for funding, NIH will request "just-in-time" information from the applicant. For details, applicants may refer to the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General (http://grants.nih.gov/archive/grants/policy/nihgps_2003/index.htm).

A formal notification in the form of a Notice of Grant Award (NGA) will be provided to the applicant organization. The NGA signed by the grants management officer is the authorizing document. Once all administrative and programmatic issues have been resolved, the Notice of Grant Award will be generated via email notification from the awarding component to the grantee business official (designated in item 14 on the Application Face Page). If a grantee is not email enabled, a hard copy of the Notice of Grant Award will be mailed to the business official.

Selection of an application for award is not an authorization to begin performance. Any costs incurred before receipt of the NGA are at the recipient's risk. These costs may be reimbursed only to the extent considered allowable pre-award costs. See also Section IV.5. Funding Restrictions.

Prior to award, the grantee and NIGMS will agree to the data and resource sharing plans, which will be specified in the NGA.

The following Terms and Conditions will be incorporated into the award statement and will be provided to the Principal Investigator as well as to the appropriate institutional official, at the time of award.

2.A. Cooperative Agreement Terms and Conditions of Award

The following special terms of award are in addition to, and not in lieu of, otherwise applicable OMB administrative guidelines, HHS grant administration regulations at 45 CFR Parts 74 and 92 (Part 92 is applicable when State and local Governments are eligible to apply), and other HHS, PHS, and NIH grant administration policies.

The administrative and funding instrument used for this program will be the cooperative agreement U24 , an "assistance" mechanism (rather than an "acquisition" mechanism), in which substantial NIH programmatic involvement with the awardees is anticipated during the performance of the activities. Under the cooperative agreement, the NIH purpose is to support and stimulate the recipients' activities by involvement in and otherwise working jointly with the award recipients in a partnership role; it is not to assume direction, prime responsibility, or a dominant role in the activities. Consistent with this concept, the dominant role and prime responsibility resides with the awardees for the project as a whole, although specific tasks and activities may be shared among the awardees and the NIH as defined above.

2.A.1. Principal Investigator Rights and Responsibilities

The Principal Investigator will have the primary responsibility for:

The design, management and maintenance of the Resource;

Proposing milestones for the project;

Organizing the annual Steering Committee Meeting;

Attending Steering Committee meetings;

Implementing the policy and guidelines approved by the Steering Committee;

Contributing to the cooperative nature of the project.

Awardees will retain custody of and have primary rights to the data and software developed under these awards, subject to Government rights of access consistent with current HHS, PHS, and NIH policies.

2.A.2. NIH Responsibilities

An NIH Project Scientist will have substantial programmatic involvement that is above and beyond the normal stewardship role in awards, as described below.

NIH Project Scientists with expertise in relevant areas will serve on the Steering Committee as representatives of the NIH extramural staff and will help guide the development of the Resource by providing overall advice and coordination. They will have responsibility for:

Facilitating the coordination of efforts of Federally supported database and resource projects that are directly relevant to the K-12 Resource;

Inviting, in consultation with the Steering Committee, non-NIH Federal officials to join the Committee;

Ensuring that the directions taken by the K-12 Resource are consistent with the NIH missions and goals; and

Making recommendations regarding support as the continuing needs of the K-12 Resource become clear and new opportunities present themselves.

NIH staff will facilitate, not direct, activities. Decisions will be reached through consensus with the Principal Investigator and other members of the Steering Committee.

Additionally, an NIGMS program official or program director will be responsible for the normal programmatic stewardship of the award and will be named in the award notice. The Program Director is a central contact for all scientific and fiscal issues and serves as a resource to the project regarding DHHS, NIH, and NIGMS recommendations and policies. The Program Director or designate will attend all Steering Committee meetings but is not a voting member of the Steering Committee.

2.A.3. Collaborative Responsibilities

The E. coli K-12 Resource Steering Committee will include representation from NIH Project Scientists and possibly other Federal officials, the awardee, and selected scientists from outside the Resource in order to gain a breadth of input into the informational needs of the experimental and bioinformatics research communities. Federal scientists will not comprise more than 40% of the voting members on the Steering Committee. The NIGMS Program Director is not a member of the Steering Committee, but will facilitate formation of the group, selecting the Chair of the Committee in consultation with the PI, and will attend all meetings. Federal officials may not serve as Chair. The Chair is responsible for developing meeting agendas, chairing meetings, and preparing a report in consultation with NIH Project Scientists. The Steering Committee decides on the schedule of meetings, at least once each year, usually in Bethesda, MD. The Steering Committee may establish subcommittees as necessary. The Steering Committee also may add members, with the approval of the NIGMS Program Director.

The Steering Committee will:

Serve as the main governing board of the K-12 Resource;

Set milestones;

Assess progress;

Develop guidelines and policies for data sharing and release to public domains;

Each full member will have one vote. Awardee members of the Steering Committee will be required to accept and implement policies approved by the Steering Committee.

2.A.4. Arbitration Process

Any disagreements that may arise in scientific or programmatic matters (within the scope of the award) between award recipients and the NIH may be brought to arbitration. An Arbitration Panel composed of three members will be convened. It will have three members: a designee of the Steering Committee chosen without NIH staff voting, one NIH designee, and a third designee with expertise in the relevant area who is chosen by the other two; in the case of individual disagreement, the first member may be chosen by the individual awardee. This special arbitration procedure in no way affects the awardee's right to appeal an adverse action that is otherwise appealable in accordance with PHS regulations 42 CFR Part 50, Subpart D and HHS regulations 45 CFR Part 16.

3. Reporting

Awardees will be required to submit the PHS Non-Competing Grant Progress Report, Form 2590 annually (http://grants.nih.gov/grants/funding/2590/2590.htm) and financial statements as required in the NIH Grants Policy Statement. The E. coli K-12 Resource Steering Committee will submit a report once a year, following the annual meeting, that will describe progress on the preceding year milestones and plans and recommendations for the Resource in the upcoming year.

Section VII. Agency Contacts

We encourage your inquiries concerning this funding opportunity and welcome the opportunity to answer questions from potential applicants. Inquiries may fall into three areas: scientific/research, peer review, and financial or grants management issues:

Sharing Research Data:
Investigators submitting an NIH application seeking $500,000 or more in direct costs in any single year are expected to include a plan for data sharing or state why this is not possible (http://grants.nih.gov/grants/policy/data_sharing).

Investigators should seek guidance from their institutions, on issues related to institutional policies and local IRB rules, as well as local, State and Federal laws and regulations, including the Privacy Rule. Reviewers will consider the data sharing plan but will not factor the plan into the determination of the scientific merit or the priority score.

Sharing of Model Organisms:
NIH is committed to support efforts that encourage sharing of important research resources including the sharing of model organisms for biomedical research (see http://grants.nih.gov/grants/policy/model_organism/index.htm). At the same time the NIH recognizes the rights of grantees and contractors to elect and retain title to subject inventions developed with Federal funding pursuant to the Bayh Dole Act (see the NIH Grants Policy Statement http://grants.nih.gov/archive/archive/grants/policy/nihgps_2003/index.htm). All investigators submitting an NIH application or contract proposal, beginning with the October 1, 2004 receipt date, are expected to include in the application/proposal a description of a specific plan for sharing and distributing unique model organism research resources generated using NIH funding or state why such sharing is restricted or not possible. This will permit other researchers to benefit from the resources developed with public funding. The inclusion of a model organism sharing plan is not subject to a cost threshold in any year and is expected to be included in all applications where the development of model organisms is anticipated.

Public Access to Research Data through the Freedom of Information Act:
The Office of Management and Budget (OMB) Circular A-110 has been revised to provide public access to research data through the Freedom of Information Act (FOIA) under some circumstances. Data that are (1) first produced in a project that is supported in whole or in part with Federal funds and (2) cited publicly and officially by a Federal agency in support of an action that has the force and effect of law (i.e., a regulation) may be accessed through FOIA. It is important for applicants to understand the basic scope of this amendment. NIH has provided guidance at http://grants.nih.gov/grants/policy/a110/a110_guidance_dec1999.htm. Applicants may wish to place data collected under this PA in a public archive, which can provide protections for the data and manage the distribution for an indefinite period of time. If so, the application should include a description of the archiving plan in the study design and include information about this in the budget justification section of the application. In addition, applicants should think about how to structure informed consent statements and other human subjects procedures given the potential for wider use of data collected under this award.

URLs in NIH Grant Applications or Appendices:
All applications and proposals for NIH funding must be self-contained within specified page limitations. Unless otherwise specified in an NIH solicitation, Internet addresses (URLs) should not be used to provide information necessary to the review because reviewers are under no obligation to view the Internet sites. Furthermore, we caution reviewers that their anonymity may be compromised when they directly access an Internet site.

Healthy People 2010:
The Public Health Service (PHS) is committed to achieving the health promotion and disease prevention objectives of "Healthy People 2010," a PHS-led national activity for setting priority areas. This PA is related to one or more of the priority areas. Potential applicants may obtain a copy of "Healthy People 2010" at http://www.health.gov/healthypeople.

Authority and Regulations: This program is described in the Catalog of Federal Domestic Assistance at http://www.cfda.gov/ and is not subject to the intergovernmental review requirements of Executive Order 12372 or Health Systems Agency review. Awards are made under the authorization of Sections 301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and under Federal Regulations 42 CFR 52 and 45 CFR Parts 74 and 92. All awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement. The NIH Grants Policy Statement can be found at http://grants.nih.gov/grants/policy/policy.htm.

The PHS strongly encourages all grant recipients to provide a smoke-free workplace and discourage the use of all tobacco products. In addition, Public Law 103-227, the Pro-Children Act of 1994, prohibits smoking in certain facilities (or in some cases, any portion of a facility) in which regular or routine education, library, day care, health care, or early childhood development services are provided to children. This is consistent with the PHS mission to protect and advance the physical and mental health of the American people.

Loan Repayment Programs:
NIH encourages applications for educational loan repayment from qualified health professionals who have made a commitment to pursue a research career involving clinical, pediatric, contraception, infertility, and health disparities related areas. The LRP is an important component of NIH's efforts to recruit and retain the next generation of researchers by providing the means for developing a research career unfettered by the burden of student loan debt. Note that an NIH grant is not required for eligibility and concurrent career award and LRP applications are encouraged. The periods of career award and LRP award may overlap providing the LRP recipient with the required commitment of time and effort, as LRP awardees must commit at least 50% of their time (at least 20 hours per week based on a 40 hour week) for two years to the research. For further information, please see: http://www.lrp.nih.gov/.